To evaluate the long-term efficacy and safety of standard-fluence photodynamic therapy (PDT) with verteporfin using the minimum PDT spot size in patients with diffuse retinal pigment epitheliopathy (DRPE). This is a retrospective study of 67 DRPE cases treated with PDT using a standardized minimum spot size of 850 μm. Indocyanine green angiography (ICGA) was used to guide and determine the outcome of PDT treatment. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), recurrences, and adverse events were recorded and analyzed. The mean follow-up period of the study was 35.8 ± 16.6 months. There was a statistically significant difference in BCVA between baseline and the end of the follow-up (p<0.001). The BCVA improved in 41 eyes (61.2%), remained stable in 20 eyes (29.9%), and deteriorated in 6 eyes (9%). Accordingly, there was a statistically significant difference in CRT between the baseline and the last follow-up visit (p<0.001). The recurrence rate was 13.4% and only one eye presented a recurrence at the same site as the laser treatment. No adverse events were noted. Application of ICGA-guided standard PDT, with a laser spot size of minimum diameter, on the site of active leakage seems to be effective and safe in a long-term follow-up period, presenting improvement in BCVA, decrease in CRT, and low rate of recurrence.